The major goal of the Mouse ore is to provide state-of-the-art transgenic and ES cell technology to support the development of authentic mouse models of human autosomal dominant polycystic kidney disease (ADPKD). Support to participating projects will be provided in four areas: 1) ES cell culture and blastocyst injection, 2) Generation of transgenic mice by micro transgenic mice by microinjection of mouse embryos, 3) Maintenance of breeding colonies and performance of genetic crosses, and 4) Genotype analysis. ES cell culture and blastocyst infection will be required for generating mice carrying a foxed Pkd2 allele that can be inactivated by Cre/lox-mediated recombination (Projects 1). Pronuclear microinjection will be required to generate transgenic mice expressing a hormone-inducible form of Cre recombinase using either a ubiquitous or kidney-specific gene promoter (Projects 1). Transgenic mice carrying a green fluorescent protein (GFP) or Pkd2 gene expression in Project 2. Genetic crosses will be performed to produce mice carrying combinations of floxed Pkd2 alleles, a Cre-estrogen receptor deluder gene, and a ROPSA26-Cre reporter gene in which inactivation of Pkd2 an be induced by hormone treatment and mutant cells can be identified by X-Gal staining. Such mice will be used to study the pathogenesis of cyst formation in adult mice (Project 1), the role of Pkd2 in kidney development (Project 2), and the alterations of membrane transport in cyst epithelium (Project 4). Mutant mice will be crossed with an SV40-transgenic mouse (ImmortoMouse) to produce mutant cell lines for studies of polycystin-2 intracellular trafficking (Project 3) and ion channel properties (Project 1). The Mouse Core will provide centralized services for animal husbandry and genotype analysis of the various mutant and transgenic strains.